Dendritic cell vaccine therapy by immunization with fusion cells of interleukin-2 gene-transduced, spleen-derived dendritic cells and tumour cells.

Abstract

We examined the preventive and therapeutic effects of fusion cells prepared from spleen-derived dendritic cells (DCs) transduced with the interleukin-2 (IL-2) gene and QRsP fibrosarcoma cells in a mouse lung metastasis model. The IL-2 or LacZ gene was introduced into spleen-derived DCs using an adenoviral vector. Irradiated QRsP tumour cells were fused with IL-2 gene-transduced DCs (fusion/IL-2) or LacZ gene-transduced DCs (fusion/LacZ) by polyethylene glycol. These fusion cells expressed major histocompatibility complexes (MHC) class I and II, CD86, CD11c and CD8alpha. Splenocytes from mice vaccinated with fusion cells showed increased production of interferon-gamma (IFN-gamma) and cytotoxic T-lymphocyte (CTL) activity as compared with those vaccinated with DCs or tumour cells alone, and CTL levels were higher in fusion/IL-2-vaccinated mice than in fusion/LacZ-vaccinated mice. In our experiments on the protective and therapeutic effects on lung metastasis, mice vaccinated with fusion/IL-2 fusion/LacZ or fusion showed a significant reduction in pulmonary metastasis compared with those given DCs, tumour or phosphate-buffered saline. The introduction of the IL-2 gene into fusion cells produced more potent preventive and therapeutic effects. These results suggest that immunization with fusion cells prepared from spleen-derived DCs and tumour cells is capable of inducing preventive and therapeutic anti-tumour immunity against lung metastasis, and modification by the IL-2 gene may increase anti-tumour efficacy.